Gut microbiota manipulation with prebiotics in patients with non-alcoholic fatty liver disease: a randomized controlled trial protocol

Jennifer E Lambert, Jill A Parnell, Bertus Eksteen, Maitreyi Raman, Marc R Bomhof, Kevin P Rioux, Karen L Madsen, Raylene A Reimer, Jennifer E Lambert, Jill A Parnell, Bertus Eksteen, Maitreyi Raman, Marc R Bomhof, Kevin P Rioux, Karen L Madsen, Raylene A Reimer

Abstract

Background: Evidence for the role of the gut microbiome in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is emerging. Strategies to manipulate the gut microbiota towards a healthier community structure are actively being investigated. Based on their ability to favorably modulate the gut microbiota, prebiotics may provide an inexpensive yet effective dietary treatment for NAFLD. Additionally, prebiotics have established benefits for glucose control and potentially weight control, both advantageous in managing fatty liver disease. Our objective is to evaluate the effects of prebiotic supplementation, adjunct to those achieved with diet-induced weight loss, on heptic injury and liver fat, the gut microbiota, inflammation, glucose tolerance, and satiety in patients with NAFLD.

Methods/design: In a double blind, placebo controlled, parallel group study, adults (BMI ≥25) with confirmed NAFLD will be randomized to either a 16 g/d prebiotic supplemented group or isocaloric placebo group for 24 weeks (n = 30/group). All participants will receive individualized dietary counseling sessions with a registered dietitian to achieve 10 % weight loss. Primary outcome measures include change in hepatic injury (fibrosis and inflammation) and liver fat. Secondary outcomes include change in body composition, appetite and dietary adherence, glycemic and insulinemic responses and inflammatory cytokines. Mechanisms related to prebiotic-induced changes in gut microbiota (shot-gun sequencing) and their metabolic by-products (volatile organic compounds) and de novo lipogenesis (using deuterium incorporation) will also be investigated.

Discussion: There are currently no medications or surgical procedures approved for the treatment of NAFLD and weight loss via lifestyle modification remains the cornerstone of current care recommendations. Given that prebiotics target multiple metabolic impairments associated with NAFLD, investigating their ability to modulate the gut microbiota and hepatic health in patients with NAFLD is warranted.

Trial registration: ClinicalTrials.gov (NCT02568605) Registered 30 September 2015.

Figures

Fig. 1
Fig. 1
Schematic overviews of the a study design and b testing day protocols. *Blood work at Calgary Laboratory Services (CLS) includes: glucose, lipids (total, LDL, HDL, TG), HbA1C, liver enzymes (ALT, AST, ALP), FibroTest (gamma-glutamyl transpeptidase, bilirubin, α2-macroglobulin, haptoglobin, and apo-lipoprotein A1), CRP, and liver function biochemistries (creatinine, electrolytes, albumin, bilirubin). **Adipokines/Cytokines include: adiponectin, MCP-1, TNF-α, IL-6 and IL-8. ***Satiety hormones include: active ghrelin, insulin, leptin, total GIP, active GLP-1, and total PYY

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